Giving smaller doses of chemotherapy more frequently may attack tumor blood supply

March 26, 2001

Radiation oncologists at Thomas Jefferson University Hospital are rethinking how to give chemotherapy, taking advantage of its unique properties. They are giving chemotherapy more frequently than usual and in tinier doses, targeting the process by which a new blood supply is created feeding tumor growth, called angiogenesis.

Traditionally, most cancer therapies are used in highest possible doses, says Adam Dicker, M.D., Ph.D., assistant professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and at Jefferson's Kimmel Cancer Center. But anti-angiogenesis drugs have caused people to rethink chemotherapy. "Instead of targeting the tumor, perhaps you can target the tumor-associated blood supply," he says.

Dr. Dicker and his Jefferson co-workers studied the chemotherapy drug docitaxel (Taxotere) in the laboratory in lower-than-usual doses, about one-tenth the clinical dose. They wanted to see the effects of radiation and the drug, which makes cancer cells more vulnerable to radiation, on endothelial cells, which are involved in angiogenesis.

They found the lower doses of drug affect different parameters of angiogenesis and can increase the effects with radiation. "This is a unique approach in combination therapy, targeting the vasculature," Dr. Dicker said.

Dr. Dicker will present the group's findings March 27 at the annual meeting of the American Association for Cancer Research meeting in New Orleans.

"What's unique about this is that we've used a common chemotherapy agent in an antiangiogenic manner and potentiated that," Dr. Dicker says. "This area is particularly interesting because these drugs, which are FDA approved, can have antiangiogenic effects.

"It's a totally new way of thinking, it's completely changed the paradigm," says Dr. Dicker. "With all the interest in anti-angiogenesis, you can rethink how you give chemotherapy and radiation."

According to Dr. Dicker, recent research have shown dramatic effects with conventional chemotherapy, but used in a different way. Instead of using large doses infrequently, every three weeks or so, for example, giving the time the body needs to recover from chemotherapy, preclinical studies have been using lower doses more frequently, maybe twice a week.

They next plan to take this approach, using low-dose docetaxel and radiation therapy, in a study in lung cancer together with colleague Maria Werner-Wasik, M.D., assistant professor of radiation oncology at Jefferson Medical College.
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Thomas Jefferson University

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